Primary Amenorrhea 2024 PDF

Primary Amenorrhea Dr.Khalida Hassan Muho Specialist OB\GYN Objectives To know the definitions of primary amenorrhoea To know the different causes for a primary amenorrhoea To know how to diagnose premature ovarian failure. To be able to approach systematically and arrange suitable i...

Primary Amenorrhea Dr.Khalida Hassan Muho Specialist OB\GYN Objectives To know the definitions of primary amenorrhoea To know the different causes for a primary amenorrhoea To know how to diagnose premature ovarian failure. To be able to approach systematically and arrange suitable investigations for a case of amenorrhoea Understand the principles of management of a case of amenorrhoea including the management of fertility problems. :Case scenario A 17-year-old girl, who may have only one kidney, present with primary amenorrhea. She denies weight loss or excessive exercise. On examination, she is 5 ft 6 in. tall and weight 140 Ib. her blood pressure is 110/60mmHg. Her thyroid gland is normal. She has appropriate Tanner stage IV breast development, axillary.and pubic hair, and female external genitalia Most likely diagnosis : Mullerian agenesis.Next step in diagnosis: Serum testosterone, or karyotype Objectives Know the definition of primary amenorrhea.1 Know the causes of primary amenorrhea.2 CLASSIFICATION OF AMENORRHEA AMENORRHEA PHYSIOLOGICAL PATHOLOGICAL Pre-puberty Primary Pregnancy related Secondary Menopause.Definition.Amenorrhea means absence of menstrual bleeding.Primary means bleeding has never occurred.Diagnosis Primary amenorrhea is diagnosed with absence of menses at age 14 without secondary sexual development.or age 16 with secondary sexual development CONTROL OF MENSTRUAL CYCLE HYPOTHALAMUS PITUITARY ENDOCRINE OVARIAN OUTFLOW TRACT AXIS The aetiology of primary amenorrhea is classify according to the presence or absence of secondary sexual characteristics. A. secondary sexual characteristics normal Imperforate hymen Transverse vaginal septum Absent vagina and functioning uterus Absent vagina and non-functioning uterus XY female: androgen insensitivity Resistant ovary syndrome Constitutional delay B. Secondary sexual characteristics absent further classified into : 1-Normal stature  Hypogonadotropnic hypogonadism  Hypergonadotropnic hypogonadism Hypogonadotropnic hypogonadism: Congenital Isolated gonadotrophin-releasing hormone deficiency Olfactogenital syndrome Acquired: Weight loss/anorexia Excessive exercise Hyperprolactinaemia Hypergonadotrophic hypogonadism Gonadal agenesis XX or XY agenesis Gonadal dysgenesis Turner mosaic Other X deletions or mosaics Ovarian failure Galactosaemia 2-Short stature:  Hypogonadotrophic hypogonadism  Hypergonadotrophic hypogonadism Hypogonadoirophlc hypogonadism Hydrocephalus Trauma Empty sella syndrome Tumors Hypergonadotrophic hypogonadism Turner syndrome Other X deletions or mosaics Clinical Approach—Preliminary Evaluation Are breasts present or absent? A physical examination will evaluate secondary sexual characteristics (breast development, axillary and pubic hair, growth). Breasts are an endogenous assay of estrogen. Presence of breasts indicates adequate estrogen production. Absence.of breasts indicates inadequate estrogen exposure Is a uterus present or absent? An ultrasound of the pelvis should be performed to assess presence of a normal.uterus  Imperforate hymen The imperforate hymen may present at two stages of development. It may present in early childhood when the infant presents with a bulging hymen behind which is a mucocele, the vagina expanded by vaginal secretions of mucus. This is easily released and does not subsequentlvy cause any problems following hymenectomy. It may also present in later life when a pubertal girl complains of intermittent abdominal pain, which is usually cyclical. The pain is due to dysmenorrhoea associated with the accumulation of menstrual blood within the vagina. The vagina is a very distensible organ and can allow quite large quantities of blood to collect in some cases. This situation is  When some blood does accumulate within the uterine cavity it is known as haematometra. As the vaginal mass enlarges there may be associated difficulty with micturition and defecation. Examination will occasionally reveal an abdominal swelling and observation of the introitus will display a tense bulging bluish  Transverse vaginal septum In circumstances where the vagina fails to cannulate, the upper and lower parts of the vagina are separate. These girls present with cyclical abdominal pain due to the development of haematocolpos, an abdominal mass may be palpable but inspection of the vagina shows that it is blind-ending and, although it may be bulging, it is pink not blue. The hymenal remnants are often seen separately. Transverse vaginal septum may occur at three levels, known as a lower, middle or upper third septum. no introital swelling may be visible and rectal examination may disclose a mass.  Absent vagina and a non- functioning uterus This is the second most common cause of primary amenorrhoea, second only to Turner's syndrome. Secondary sexual characteristics are normal, ovarian function is unaffected. Examination of the genital area discloses normal female external genitalia but blind- ending vaginal dimple which is usually not more than 1.5 cm in depth. This is known as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome and uterine development is usually absent. Often small uterine remnants (anlage) are found on the lateral pelvic side walls. It is important to remember that 40% of these patients have renal anomalies, for example an absent kidney, and skeletal abnormalities associated with this syndrome.  Absent vagina and the functioning uterus This is a rare phenomenon when embryologicaliy the uterine body has developed normally but there is failure of development of the cervix. This leads to failure of the development of the upper vagina. The presenting symptom is again cyclical abdominal pain, but there is no pelvic mass to be found because there is no vagina, to be distended. Although a small  XY female( androgen insensitivity ) In androgen insensitivity there is a structural abnormality of the androgen receptor, due to defects in the androgen receptor gene, which results in a non-functional receptor. This means that the masculinizing effect of testosterone during normal development is prevented and patients are therefore  phenotypically female with normal Pubic hair is very scanty in these patients as there is no androgen response in target tissues. The vulva is normal and the vagina is usually short. The uterus and tubes are absent.  The testes are usually found in the lower abdomen, but occasionally may be found in hernial sacs in childhood.  Resistant ovary syndrome This is an extremely rare cause of primary amenorrhoea. There are elevated levels of gonadotrophin in the presence of apparently normal ovarian tissue. these women have an absence or malfunction of FSH receptors in the ovarian follicles.  Constitutional delay Normal secondary sexual characteristics. There is no anatomical anomaly and endocrine investigations are all normal. These young women are found to have immature pulsatile release of GnRH and they menstruate spontaneously as the maturation process proceeds. B.Absent secondary sexual characteristics (normal height)  Isolated GnRH deficiency (olfactogenital syndrome, Kallman's syndrome) The hypothalamus lacks the ability to produce GnRH and there is therefore a hypogonadotrophic state due to maldevelopment of neurones in the arcuate nucleus of the hypothalamus. These neurones are derived embryologically from the olfactory bulb and therefore some patients may also have failure of development of the ability to smell (anosmia). When this occurs it is known as Kallman's syndrome.  Weight loss/anorexia Weight loss is more commonly associated with secondary amenorrhoea than primary amenorrhoea, anorexia nervosa in the prepubertal state leads to failure of activation of the gene which initiates GnRH release in the hypothalamus, and therefore a persistent hypogonadotrophic state exists. The growth spurt is  Excessive exercise  excessive exercise in pubertal children leads to decreased body fat content, without necessarily affecting body mass, including ballet dancers, athletes and gymnasts.  Hyperprolactinaemia This is an unusual cause of primary amenorrhoea and is much more commonly seen as a cause of secondary amenorrhoea. There may be a recognizable prolactinoma in the  Gonadal agenesis there is complete failure of development of the gonad. These girls may be either 46XX or 46XY The 46XX pure gonadal dysgenesis is an autosomal recessive disorder , in all these patients their genotype does not affect their phenotype, all of them being female.  Gonadal dysgenesis The commonest is Turner's syndrome, is a single X chromosome giving a 45X karyotype. There are other circumstances in which the gonadal dysgenesis may be associated with a mosaic. Here two cell lines exist within one individual, the most common being 45X/46XX, Other structural chromosomal anomalies associated with gonadal dysgenesis involve deletions.  Ovarian failure ovarian failure as a result of either chemotherapy or radiotherapy for childhood malignancy  Galactosaemia This inborn error of galactose metabolism is due to deficiency of galactose-1 -phosphate uridyltransferase. Patients have an acute toxic syndrome that causes ovarian cellular destruction thought to be due to the accumulation of B.Absent secondary sexual characteristics (short stature)  Congenital infection,The most common aetiology is hydrocephalus, as a result of childhood or neonatal infection lead to damages the hypothalamus, (hypogonadotrophic hypogonadic state).  Trauma to the skull base may also damage the hypothalamus and prevent GnRH secretion.  Empty sella syndrome , congenital absence of the pituitary gland or at least part of it, leading to failure to produce gonadotrophins.  Tumors: pituitary tumors like crainopharyngiorna in childhood result in destruction of pituitary gland.  Turner's syndrome In pure Turner's syndrome the chromosome complement is 45X and here a syndrome of short stature and ovarian failure lead to the typical features. Diagnosis "primary amenorrhea” 1 -History 2 -Exam 3 -Investigation 4 -Workup  History in primary amenorrhea *Developmental milestones (age of growth spurt ,age of thelarche, adrenarche) *congenital infection, Trauma, Tumor *Cyclic symptoms of menstruation *Weight changes. *Excessive exercise *History of anosmia *A history is taken including a family history as AIS may affect other females in the family.  Physical examination. The general examination should begin by recording the girl’s height—if by 16 she is less than 147 cm there is a possibility of ovarian agenesis (Turner’s syndrome) or (pan)hypopituitarism. If there is a decrease in body weight, calculate Body Mass Index (wt(kg)/ht(m2)). A general examination checks the development of secondary sexual characteristics, hair patterns and density.  A pelvic examination should be performed if the examiner really thinks a positive finding will be there. The vulva is inspected to see that the introitus is patent; there may be cryptomenorrhoea, congenital absence of the vagina or a blind vagina as in AIS. Investigations a buccal smear and an examination of the polymorphonuclear leucocytes to determine if chromatin positive (probably XX) or chromatin negative (probably XO or XY); in other cases a full chromosome analysis may be needed to exclude mosaicism and AIS. Hormonal investigations should include LH, FSH, prolactin ,oestradiol and testosterone levels. Ultrasound will help determine the presence, state and size of the ovaries and any follicular activity. Uterine size can also be seen. It is rarely necessary to perform a laparoscopy to assess the pelvic organs.  Evaluation and management most of the conditions are rare and constitutional delay is undoubtedly the most common diagnosis. However ,this diagnosis of constitutional delay should only be made when all other syndromes have been excluded.  Patients with an absent uterus require special psychological counselling and their care should be managed in a centre able to offer the complete range of psycho­logical, psychosexual and gynaecological expertise. At the appropriate time a vagina may be created either non-surgically or surgically. In 85% of cases the use of vaginal dilators is successful.  In girls found to have an XY karyotype, careful counselling is necessary over the malignant potential of their gonads, this being reported in around 30%. It is therefore necessary for them to have their gonads removed and this must be performed at a time when counselling is complete.  In outflow tract obstruction, surgical management may occur at various levels. The simplest form is an imperforate hymen and in this condition a cruciate incision in the hymen allows drainage of the retained menstrual blood. Transverse vaginal septae are much more difficult to deal with and require specialist reconstruction to create a vagina  If investigations suggest constitutional delay and development of secondary sexual characteristics is complete, there is no need to suggest any treatment other than annual review. In some circumstances it may be useful to promote a menstruation using the oral contraceptive pill for one cycle to prove that menstruation can occur and this can be extremely reassuring.  If the diagnosis of resistant ovary syndrome is suspected, then diagnosis can really only be made by ovarian biopsy and subsequent histology confirming or illustrating the absence of oocytes. Finally, elevated prolactin levels should provoke the clinician to perform imaging of the pituitary fossa, probably best done by CT, to determine the presence or absence  Evaluation of Primary Amenorrhea History and physical examination completed for a patient with primary amenorrhea Secondary sexual characteristics present No Yes Measure FSH and LH levels Perform ultrasonography of uterus FSH and LH FSH > 20 IU/ L and Uterus absent Uterus present < 5 IU/ L LH > 40 IU/ L or abnormal or normal Hypergonadotropic Karyotype Hypogonadotropic hypogonadism Outflow obstruction hypogonadism analysis Yes No Karyotype analysis ,46 ,46 XY XX Evaluate for secondary CNS; HP amenorrhea Disorder Androgen Mullerian Gonadal AgenesisImperforate insensitivit Failure hymen or y transverse Syndrome vaginal septum Mullerian agenesis Androgen insensitivity Axillary and pubic hair normal scant or absent Testosterone level female male Karyotype 46XX 46XY Uterus absent Idiopathic MIF Estrogen from ovaries peripheral conversion Treatment no hormones estrogen create vagina create vagina Complications renal anomalies remove testes Gonadal dysgenesis HP Axis failure FSH Increase decrease Karyotype 45X 46XX Ovaries steak normal Why no estrogen no ovarian follicles follicles not stimulated Treatment E+P E+P Pregnancy egg donor induce ovulation(HMG) Thank you